Tissue trauma in the peritoneal and pelvic cavities following surgery or bacterial infection results in adhesions that are a debilitating cause of intestinal obstruction, chronic pelvic pain, and infertility in women. During the response to surgical trauma, unchecked fibrosis leads to the development of fibrous adhesions that bind apposing tissues together in an inappropriate manner. Surgical adhesions are a major complication of gynecologic and abdominal surgery, with an incidence as high as 50-90% (Trimbos-Kemper et al., Fertil Steril 43:395-400 (1985); Monk et al., Am. J. Obstet. Gynecol. 170:1396-1403 (1994); Lower et al., Brit. J. Obstet. Gynaecol. 107:855-862 (2000)). Adhesions that develop after gynecologic surgery are a source of chronic pelvic pain and infertility (Lower et al. (2000)). In addition, most severe adhesions in the abdominal cavity can cause potentially fatal small bowel obstruction and organ failure (Ellis, Eur. J. Surg. Suppl. 577: 5-9 (1997); Wilson et al., Br. J. Surg. 85:1294-1298 (1998); Diamond et al., Hum. Reprod. Update 7:567-576 (2001).
Adhesion generally occurs as a result of the normal wound healing response within days after injury. The molecular and cellular mechanisms involved in the development of adhesions are not fully understood. It has been reported that Th1 CD4+ T cells were critical to adhesion formation and orchestrate host response after peritoneal injury (Chung et al., J. Exp. Med. 195:1471-1478 (2002)).
Current treatments to prevent or reduce the severity of adhesions rely primarily on the use of barrier devices or bioresorbable gels. However, effective adhesion reduction by physical barriers may be limited to the site of application (J. Gastrointest Surg 13:35-42, 2009). Anti-inflammatory drugs such as corticosteroids and non-steroids, and protease inhibitors, have also been utilized in adhesion prevention (Clin. Exp. Gynecol. 28: 126-127, 2001; US Publication 2006/0122101A1). However, systemic or intraperitoneal administration of corticosteroids, while reducing adhesion formation, also severely compromises wound healing and causes immunosuppression in post-surgical patients.
There remains a need for an effective approach to prevent and inhibit formation of adhesion.